QEEN II: 2ND QUANTIFYING EXPOSURE TO ENGINEERED NANOMATERIALS FROM - - PowerPoint PPT Presentation

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QEEN II: 2ND QUANTIFYING EXPOSURE TO ENGINEERED NANOMATERIALS FROM MANUFACTURED PRODUCTS WORKSHOP SESSION B. CONSUMER EXPOSURE: FOOD, FOOD CONTACT, AND PERSONAL CARE PRODUCTS Cytotoxicity, hemotoxicity, and in-vivo toxicity of surface modified

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Washington DC, October 8-10

QEEN II: 2ND QUANTIFYING EXPOSURE TO ENGINEERED NANOMATERIALS FROM MANUFACTURED PRODUCTS WORKSHOP SESSION B. CONSUMER EXPOSURE: FOOD, FOOD CONTACT, AND PERSONAL CARE PRODUCTS

Cytotoxicity, hemotoxicity, and in-vivo toxicity of surface modified PLGA nanoparticles Cristina M. Sabliov, LSU Alumni Professor

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Engineered nanoparticles

Chou, L. Y. T, K. Ming and W. C. W. Chan. 2011. Chem. Soc. Rev. 40, 233-245.

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Yu Yang, Paul Westerhoff. 2014. Nanomaterial Impacts on Cell Biology and Medicine, pp 1 – 17. Part of the Advances in Experimental Medicine and Biology book series (volume 811).

Exposure

Intentional exposure
Fortified foods
Unintentional exposure
Packaging
Agrochemical nanodelivery systems

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Particle ADME profile

Picture drawn by Thanida Chuacharoen Cockburn et al., 2012

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D.Shevlin, N.O'Brien, E.Cummins. 2018. Science of the Total environment. April, 2018.

Particle Biotransformation

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PLGA 33K pH 6.5

0 hrs 6 hrs 24 hrs

PLGA-Chi 20 K & 33K pH 6.5

pH stability (pH=6.5)

Murugeshu, A., C. E. Astete, C. Leonardi, and C. M. Sabliov. 2011. Nanomedicine Vol. 6, No. 9, Pages 1513-1528.

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Cytotoxicity

Trif, M, P. E. Florian, A. Roseanu, M. Moisei, O. Craciunescu, C. E. Astete and C. M. Sablio

liov. 2015. Journal of Biomedical Materials Research Part A. 103(1):3599-3611

Alqahtani, S., L. Simon, C. E. Astete, A. Alayoubi, P. W. Sylvester, S. Nazzal, Y. Shen, Z. Xu, A. Kaddoumi, C. M. Sabliov. 2015. Journal of Colloid and Interface Science. 445: 243-251.

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Nanoparticles RBC Association (SEM Image)

Untreated red blood cells Red blood cells with 2mg/ml NPs Red blood cells with 3mg/ml NPs Red blood cells with 10mg/ml NPs Red blood cells with 50mg/ml NPs

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Hemotoxicity

0.22 13.95 17.41 23.32 29.92 37.21 49.71 73.46 16.74 17.26 16.22 17.65 17.78 18.56 22.45 35.43 94.48 15 30 45 60 75 90 Negative Control 2 3 5 8 10 20 50 Positive Control Percentage Nanoparticle Concentration (mg/ml)

NP Association Hemolysis Hemolysis

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In-vivo biodistribution

PLGA PLGA-Chi 7 days 14 days 21 days

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Lung Heart Brain mg NP after 7 days % daily dose Organ

PLGA 7 days (% daily dose) PLGA 7 days (mg)

(a)

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Heart Lung Brain mg Np after 7 days % daily doe Organ

PLGA/Chi 7 days (% daily dose) PLGA/Chi 7 days (mg)

(d)

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Lung Heart Brain mg Np after 14 days % daily dose Organ

PLGA 14 days (% daily dose) PLGA 14 days (mg)

(b)

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Heart Lung Brain mg NP after 14 days % daily dose Organ

PLGA/Chi 14 days (% daily dose) PLGA/Chi 14 days (mg)

(e)

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Lung Heart Brain mg NP after 21 days % daily dose Organ

PLGA 21 days (% daily dose) PLGA 21 days (mg)

(c)

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 10 20 30 40 50 Int Liver Kidney Spleen Heart Lung Brain mg NP after 21 days % daily dose Organ

PLGA/Chi 21 days (% daily dose) PLGA/Chi 21 days (mg)

(f)

Navarro, S. T. Morgan, C. E. Astete, R. Stout, D. Coulon, P. Mottramand C. M. Sablio

liov. 2016.. Nanomedicine.11(13):1653-1669. (doi: 10.2217/nnm-2016-0022)

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Liver Spleen Intestinal villi Intestinal crypts Control PLGA NPs

Liver 14 days PLGA treatment shows increased numbers of lymphocytes, plasma cells (black arrow) and occasional mast cells (white arrow). No significant lesions have been

bserved in spleen.

Intestine villi show the presence of scattered lymphocytes (blue arrow), plasma cells (red arrow) and histiocytic cells (white arrow) in the lamina propria. Arrows indicate scattered mitotic figures (black arrows). Increased hyperplasia of intestinal crypt cells indicated increased intestinal mucosal epithelial cell turnover.

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Conclusions

PLGA NPs were not cytotoxic, except at high concentration (>5 mg/ml)
Interaction between PLGA nanoparticles and RBCs was concentration

dependent

PLGA nanoparticles associated with RBC membrane and had no hemotoxic

effect at concentrations lower than 5 mg/ml (>5% increased over negative control), and was dependent on the surfactant

Minimal inflammatory changes were observed in the hepatic portal

regions of the liver and the lamina propria of the small intestine in PLGA and PLGA-Chi dosed rats versus controls

The intestine had mild crypt hyperplasia, indicative of an increased

intestinal mucosal epithelial turnover rate

No significant histologic lesions were seen in the lung, kidney, spleen, or

brain in PLGA or PLGA-Chi dosed rats versus controls

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THANK YOU!

Properties of nanomaterial still important and should be

documented

Nanomaterial biotransformation is key to in-vivo behavior
Toxicity work is mainly focused on inorganic, metal and

metal oxides nanoparticles

Interest is growing in biodegradable particles
Methods of detection of biodegradable particles in

complex media need to be developed

Toxicity testing needed for long term, small concentration

exposure is needed